Control of nasal congestion



United States Patent 3,236,729 CQNTROL OF NASAL CONGESTION Lester Colby Dick, Rye, N.Y., assignor to Richardson- Merrell Inc, New York, N.Y., a corporation of Delaware No Drawing. Filed Aug. 3, 1961, Ser. No. 128,985 6 Claims. (Cl. 16758) This invention relates to methods of and compositions for the control of nasal congestion.

Uncomfortable nasal congestion usually exists in patients with colds, hay fever, chronic allergic rhinitis, and other disturbances which cause dilation of the capillary blood vessels of the nasal passage. Decongestion is usually attempted by application of drops or sprays of liquids containing sympathornimetic amines or vasoconstrictors to the congested mucous lining. These treatments are short lasting in that the vasoconstrictors contact only the outer surface of the congested area and are quickly washed away by the natural secretions of the mucous membranes. The flow of these secretions is usually increased by whatever may be the cause of the congestion and also by the initating effect of the vasoconstrictor itself. Certain of the sympathomimetic amines may be taken orally 01' administered by injection, but these routes of administration have a number of disadvantages.

I have discovered that the oil soluble sympathomimetic amines are percutaneously absorbed when applied to the skin, and efi'ective amounts of the drug can in this manner be introduced into the circulatory system and become effective as nasal decongestants. This is particularly surprising in view of the fact that the usual forms of these sympathomimetic amines, the oil insoluble inorganic acid addition salts such as the sulfates, hydrochlorides, phosphates and the like, are not eifective as nasal decongestants when applied in the same manner.

To illustrate the present invention in greater particularity, a petrolatum based ointment was prepared by melting 85.5 parts by weight of petrolatum and adding to it at a temperature of 50 C. 14 parts by weight of an aromatic mixture consisting of menthol, camphor, eucalyptol, and oil of pine and 0.5 part by weight of l-desoxyephedrine. The thoroughly mixed solution was cooled to 43 C. and poured into a suitable container and then allowed to cool to room temperature.

A number of patients suffering from nasal congestion due to hay fever were selected and the resistance of air through their nostrils was determined by means of an apparatus which is described in the Annals of Otolaryngology, page 309, Volume 38, 1943. The apparatus consists primarily of an air pump supplying 7.6 liters to the airways, an amount which approximates the normal air intake per minute. A nasal tip is inserted in one nostril and the resistance to the flow of air is measured on a draft gauge. The average of five consistent readings is used as the resistance value. The test is repeated upon the opposite nostril and the results recorded.

After determining the resistance of the nasal airways to the passage of air, 7.5 grams of the above described ointment were rubbed onto the chest and back of each patient over an area of approximately 60 square inches. Thirty minutes after the initial air resistance measurement, the test was repeated on each nostril as before. It was found that the air resistance had decreased to 78% of the original reading on an average of all patients taking the test. After sixty minutes, the test was again repeated and this time it was found that the air resistance was only about 60% of the original reading. At the end of two hours, the test was repeated again and the average readings showed a resistance of about 68% of the original values.

In order to determine whether or not the decongestant action might be entirely due to inhalation of the various vasoconstrictors, 7.5 grams of the above described ointment were placed on aluminum foil laid on water in a water bath controlled to body temperature, 37 C. :L2 C., and patients were asked to inhale the vapors from a distance of from 6 to 10 inches for 15 minutes. It was found that after 30 minutes the resistance to air passage through the nostrils had decreased only to 95% of the original reading and after one hour with an additional 15 minute period of inhalation had decreased only to 88% of the original. These figures indicate that although some benefit can be expected by inhalation, the most important reduction in the nasal congestion is by systemic absorption of the vasoconstrictor, as shown by the greater degree of nasal dccongestion produced, when the ointment was applied to the chest and back of patients. This was further verified by finding that applications of the ointment on the legs, so that the material was at a distance from the nostrils, was also effective in bringing about decongestion.

The preferred embodiment of the present invention is to incorporate the sympathomimetic amine base in an inert petrolatum in which the amine base is dispersible and which can be readily applied to the skin. The amount of sympathomimetic amine may vary from about 0.10 to 2% by weight. Aromatics may be added to the ointment, if desired, up to 20% by weight of the ointment. It will be understood, of course, that the petrolatum can be replaced by other carriers which are commonly used in preparing salves and ointments of various kinds such as polyalkylene glycols, glycerols monostearate, stearyl alcohol, cetyl alcohol, isopropyl myristate, alginates, gums, lanolin and so forth.

It is necessary that the sympat-homimetic amine be applied to the skin in the form of its free base or an oil soluble therapeutically effective derivatives if it is to be effectively absorbed. Accordingly, compositions which contain water should also have a buffer to maintain the pH within the range 6.8 to 7.8 to insure against formation of oil insoluble salts. One such composition is prepared as follows.

The following are mixed together and heated to within the range 50 C. to C2 Parts by weight These liquid materials are poured into 50 to 75 parts by weight of water, heated to the same temperature, and the mixture is homogenized with vigorous agitation. The stirring is continued until the mixture is homogeneous and the temperature has been reduced to 45 C. At that time 0.10 to 2 parts by weight of a desired sympathomimetic amine, free base, is :added and the stirring continued until the pour point is reached which is within the range 30 C. to 43 C. This emulsion may be applied in the same manner as the ointment and is also efiective in reducing nasal congestion.

Any of the non-toxic sympathomirnetic amines which are eifective as nasal decongestants and are soluble in the oils of the skin, such as l-desoxyephedrine, propylhexedrine, phenylpropanolamine, ephedine and the oil soluble salts such as l-desoxyephedrine salicylate or the like, can be used in preparing the new composition of the present invention. The amounts of oil soluble sympathomimetic amine in the ointment may vary from about 0.10 to 2% by weight.

The skin oils include the triglycerides of fatty acids such as palmitic, stearic and oleic. They also contain some free fatty acids, fatty acids esterified with cholesterol, wax alcohols and the like and squalene.

Although the above example represents a preferred embodiment of the invention, the amount of ointment to be applied to the skin of a patient will vary with the size of the patient and the concentration of sympathomimetic amine in the ointment. Ordinarily it will be from about 1 gram to about 20 grams and should be applied over an area of approximately to 200 square inches of skin at each application, which should be repeated as necessary but not more often than once in about every eight hours. In general, the application of the sympathomimetic amine to the skin of a patient will range from about 0.1 to 2 mg. per kilogram of body weight.

I claim:

1. A method of reducing congestion of the nasal passages which comprises applying to the skin of a congested subject over an area of from 25 to 100 square inches of skin surface an ointment containing l-desoxyephedrine, said sympathomimetic amine being dispersed in a carrier in amounts ranging from 0.10 to 2.0 percent by Weight.

2. A method for reducing congestion of the nasal passages which comprises applying to the skin of a congested subject over an area from about 10 to 200 square inches of skin surface, a mixture of l-desoxyephedrine free base and aromatics dispersed in petrolatum, said mixture comprising from about 0.1 to 2.0% by weight of l-desoxyephedrine and up to about by Weight of aromatics.

3. A method of reducing congestion of the nasal passages which comprises applying l-desoxyephedrine to the skin of a congested subject over an area from about 10 to 200 square inches of skin surface, said l-desoxyephedrine dispersed in a carrier in amounts ranging from 0.10 to 2.0 percent by weight.

4. A method of reducing congestions of the nasal passages which comprises applying propylhexedrine to the skin of a congested subject over an area from about 10 to 200 square inches of skin surface, said propylhexedrine dispersed in a carrier in amounts ranging from 0.10 to 2.0 percent by weight.

5. A method of reducing congestion of the nasal passages which comprises applying a salt of l-desoxyephedrine to the skin of a congested subject over an area from about 10 to 200 square inches of skin surface, said salt being soluble in the oils of the skin and dispersed in a carrier in amounts ranging from 0.10 to 2.0 percent by weight.

6. A method of reducing congestion of the nasal passages which comprises applying a salt of propylhexedrine to the skin of a congested subject over an area from about 10 to 200 square inches of skin surface, said salt being soluble in the oils of the skin and dispersed in a carrier in amounts ranging from 0.10 to 2.0% by weight.

References Cited by the Examiner UNITED STATES PATENTS 2,785,103 3/1957 Tabern 167-54 FOREIGN PATENTS 385,148 12/1932 Great Britain.

OTHER REFERENCES Chemical Abstracts, Vol. 45, page 7298 (1951) (abstract of Seki, Ja. Iour. Pharm. & Chem, 23, 138-42, 1951).

Macht, J.A.M.A., 110, pages 409-14, 1938.

Modern Drug Encyclopedia and Therapeutic Index, 7th Edition, 1958, page 774.

Modern Drug Encyclopedia and Therapeutic Index, 7th Edition, 1958, page 1182.

United States Dispensatory, 24th Edition, 1947, page 1617.

Valette, Societe De Biologic, Vol. 139, pages 906907, Oct. 13, 1945.

LEWIS GOTTS, Primary Examiner.

MORRIS O. WOLK, FRANK CACCIAPAGLIA, JR.,

Examiners. 

1. A METHOD OF REDUCING CONGESTION OF THE NASAL PASSAGES WHICH COMPRISES APPLYING TO THE SKIN OF A CONGESTED SUBJECT OVER AN AREA OF FROM 25 TO 100 SQUARE INCHES OF SKIN SURFACE AN OINTMENT CONTAINING 1-DESOXYEPHEDRINE, SAID SYMPATHOMIMETIC AMINE BEING DISPERSED IN A CARRIER IN AMOUNTS RANGING FROM 0.10 TO 2.0 PERCENT BY WEIGHT. 